We propose a collaborative research program to carry out field studies of bacterial enteric vaccine candidates in Santiago, Chile in conjunction with the Servicio de Salud Metropolitano Norte, the Universidad de Chile, Roberto del Rio Children's Hospital and the Ministry of Health. The studies will attempt to optimize oral immunization so that young children can be successfully immunized with a single dose of vaccine. Projected studies would investigate the clinical acceptability and immunogenicity of single-dose live oral recombinant cholera vaccine strain CVD 103-HgR in toddlers and infants. If a single dose of this oral vaccine is indeed well-tolerated and immunogenic in young infants, this would provide support for the concept of the Children's Vaccine Initiative. A number of oral vaccines (e.g., attenuated poliovirus vaccine) exhibit diminished immunogenicity in low socioeconomic level children in less-developed countries. Using CVD 103-HgR as a model, we will investigate the hypothesis that such diminished immunogenicity is in part due to small bowel bacterial overgrowth (environmental enteropathy). We will perform non-invasive breath H2 tests in Santiago schoolchildren to screen for small bowel bacterial overgrowth, prior to administering a dose of CVD 103-HgR vaccine to the children. The magnitude of the vibriocidal antibody response will be compared in children with and without small bowel overgrowth. Studies will be carried out in young children to establish the safety and immunogenicity of multivalent vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC), important pathogens of diarrhea disease among children in developing countries. The ETEC vaccine will be a live vector vaccine in which ETEC colonization factor fimbriae and B subunit of heat-labile enterotoxin are expressed in attenuated live vectors. By maintaining prospective surveillance at two health centers that serve large populations of low socioeconomic level, we shall prepare a field site in which we propose to carry out a large-scale field trial of efficacy of a multivalent vaccine against Shigella or ETEC. The groups of U.S. and Chilean investigators and their institutions have a long history of productive and harmonious collaboration.